Downloads: 396

Files in This Item:
File Description SizeFormat 
j.ymgme.2010.12.009.pdf622.12 kBAdobe PDFView/Open
Full metadata record
DC FieldValueLanguage
dc.contributor.authorTanaka, Daisukeen
dc.contributor.authorNagashima, Kazuakien
dc.contributor.authorSasaki, Mayumien
dc.contributor.authorYamada, Chizumien
dc.contributor.authorFunakoshi, Shogoen
dc.contributor.authorAkitomo, Kimiyoen
dc.contributor.authorTakenaka, Katsunobuen
dc.contributor.authorHarada, Koujien
dc.contributor.authorKoizumi, Akioen
dc.contributor.authorInagaki, Nobuyaen
dc.contributor.alternative稲垣, 暢也ja
dc.description.abstract[Objective]:The aim was to investigate the genetic background of familial clustering of type 2 diabetes. [Subjects and methods]:We recruited Japanese families with a 3-generation history of diabetes. Genome-wide linkage analysis was performed assuming an autosomal dominant model. Genes in the linkage region were computationally prioritized using Endeavour. We sequenced the candidate genes, and the frequencies of detected nucleotide changes were then examined in normoglycemic controls. [Results]:To exclude known genetic factors, we sequenced 6 maturity onset diabetes of the young (MODY) genes in 10 familial cases. Because we detected a MODY3 mutation HNF1A R583G in one case, we excluded this case from further investigation. Linkage analysis revealed a significant linkage region on 2p25-22 (LOD score = 3.47) for 4 families. The 23.6-Mb linkage region contained 106 genes. Those genes were scored by computational prioritization. Eleven genes, i.e., top 10% of 106 genes, were selected and considered primary candidates. Considering their functions, we eliminated 3 well characterized genes and finally sequenced 8 genes. GCKR ranked highly in the computational prioritization. Mutations (minor allele frequency less than 1%) in exons and the promoter of GCKR were found in index cases of the families (3 of 18 alleles) more frequently than in controls (0 of 36 alleles, P = 0.033). In one pedigree with 9 affected members, the mutation GCKR g.6859C>G was concordant with affection status. No mutation in other 7 genes that ranked highly in the prioritization was concordant with affection status in families. [Conclusions]:We propose that GCKR is a susceptibility gene in Japanese families with clustered diabetes. The family based approach seems to be complementary with a large population study.en
dc.publisherElsevier Inc.en
dc.rights© 2010 Elsevier Inc.en
dc.rightsThis is not the published version. Please cite only the published version.en
dc.subjectGenetic susceptibilityen
dc.subjectLinkage analysisen
dc.titleGCKR mutations in Japanese families with clustered type 2 diabetes.en
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleMolecular genetics and metabolismen
dcterms.accessRightsopen access-
Appears in Collections:Journal Articles

Show simple item record

Export to RefWorks

Export Format: 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.